References
- 1a
Lee S.-k.
Lee SY.
Park YS.
Synlett
2001,
1941
- 1b
Caddick S.
Afonso CAM.
Candeias SX.
Hitchcock PB.
Jenkins K.
Murtagh L.
Pardoe D.
Santos AG.
Treweeke NR.
Weaving R.
Tetrahedron
2001,
57:
6589
- 1c
Ben RN.
Durst T.
J. Org. Chem.
1999,
64:
7700
- 1d
Kubo A.
Kubota H.
Takahashi M.
Nunami K.
J. Org. Chem.
1997,
62:
5830
- 1e
Ward RS.
Pelter A.
Goubet D.
Pritchard MC.
Tetrahedron: Asymmetry
1995,
6:
93
- 2 This term was used by Prof. Peter Beak and coworkers for their mechanistic studies
of electrophilic asymmetric substitution reaction:
Beak P.
Basu A.
Gallagher DJ.
Park YS.
Thayumanavan S.
Acc. Chem. Res.
1996,
29:
552
- 7a For a quantitative analysis of the reactions of two interconverting diastereomeric
species that lead to different products by a Curtin-Hammett-Winstein-Holness prin-ciple,
see:
Seeman JI.
Chem. Rev.
1983,
83:
83
- 7b For cases in which the stereoselectivity of the product reflects the thermodynamic
ratios of diastereomeric intermediates, see:
Gately DA.
Norton JR.
J. Am. Chem. Soc.
1996,
118:
3479
- 7c Also see:
Basu A.
Gallagher DJ.
Beak P.
J. Org. Chem.
1996,
61:
5718
3
(S,S)-N-Methyl pseudoephedrine is commercially available and can also be easily prepared
by N-methylation of (S,S)-pseudoephedrine with MeI and NaH.
4
When a solution of 1 (αS:αR = 67:33) in CH3CN was stirred for 1.5 h, spontaneous epimerization provided 1 with a ratio of 80:20 (αS:αR).
5
The absolute configurations of (αS)-1 was assigned by com-parison to the 1H NMR of authentic diastereomer prepared from commercially available (S)-α-bromo-propionic acid. The absolute configuration of (R)-2 was assigned by com-parison of CSP-HPLC retention time with authentic material prepared
from (R)-alanine.
6
It has been proposed by several examples that the epimeri-zation of α-halo ester and
α-halo amide can be promoted by a base via keto-enol tautomerism and/or by a halide
source via nucleophilic displacement of the bromide ion.
[1]
8
The absolute configuration of (R)-7 was assigned by comparison of CSP-HPLC retention time with authentic material prepared
from commercially available (R)-2-aminobutyric acid. The absolute configuration of (R)-8 was assigned by analogy to the formation of (R)-2 and (R)-7.
9
General procedure for the asymmetric synthesis of methyl-
N
-benzyl alaninate [(
R
)-2]: To a solution of (αRS)-1 (αS:αR = 60:40) in CH3CN (ca. 0.1 M) at r.t. was added Et3N (1.2 equiv). The resulting reaction mixture was stirred at r.t. for 1.5 h, and then
benzylamine (1.2 equiv) was added. After 4 h, the mixture was filtered and the solvent
eva-porated. The crude mixture and p-toluenesulfonic acid (0.1 equiv) in methanol were refluxed for 24 h. The solvent
was evaporated and the crude material was purified by column chromatography to give
methyl-N-benzyl alaninate [(R)-2]. From 100 mg of 1, 53 mg (86% isolated yield) of 2 was obtained as a colorless oil. 1H NMR (CDCl3, 400 MHz) 7.32-7.23 (m, 5 H), 3.80 (d, J = 12.8 Hz, 1 H), 3.72 (s, 3 H), 3.67 (d, J = 12.8 Hz, 1 H), 3.39 (q, J = 7.0 Hz, 1 H), 1.85 (br, 1 H), 1.32 (d, J = 7.0 Hz, 3 H); 13C NMR (CDCl3, 100 MHz) 176.6, 140.1, 128.8, 128.6, 127.5, 56.3, 52.4, 52.2, 19.5. The enantiomeric
ratio of 2 was determined to be 98:2 in favor of the R enantiomer by chiral HPLC using racemic material as a standard and the absolute configuration
was assigned by comparison of CSP-HPLC retention time with authentic material prepared
from (R)-alanine. [Chiralcel OD column; 10% 2-propanol in hexane; 0.9 mL/min; the R-enantio-mer(major) had a retention time of 6.0 min, and the
S-enantiomer(minor) had a retention time of 5.4 min].
